The present invention relates to improved methods and apparatus for determining differences between CO.sub.2 levels in a specific organ or region of the body of a mammalian subject and systemic CO.sub.2 levels in the blood of the subject.
Regional CO.sub.2 measurements are typically obtained from the mucosa or other tissue found in an organ or region of the body, for example, the gastrointestinal tract or urinary bladder. One way of obtaining such measurements is to place a tonometric catheter having a sampling chamber permeable to CO.sub.2 in a hollow organ of the body, such as the stomach or intestine, so that the sampling chamber is contiguous with the mucosa of the gut. A fluid sampling medium is supplied to the sampling chamber through a tube. The sampling medium receives CO.sub.2 which passes from the mucosa into the sampling chamber. The sampling medium is then removed from the chamber through the tube and the regional CO.sub.2 level is measured by suitable gas analysis means. See for example published PCT application PCT/US94/02953 and corresponding U.S. national stage application Ser. No. 08/433,398, filed May 18, 1995 describing catheters of this type and their uses. The measurement is typically expressed as a regional CO.sub.2 partial pressure (PrCO.sub.2).
Regional tonometric measurements provide an indication of the condition of the organ. It is becoming more fully appreciated that tonometric measurements, such as gastrointestinal measurements, can be used to provide an early indication or warning of serious physiological conditions which may be difficult to otherwise diagnose. Such conditions include dysoxia (deficiency in oxygen delivery), hypovolemia (abnormally decreased volume of circulating fluid in body), sepsis, and shock. The early indication arises from the fact that the gastrointestinal tract is the first organ of the body to be affected by such a condition as reflected in reduced mucosal perfusion (blood flow) in the gastrointestinal tract. The reduced perfusion in turn, increases the regional CO.sub.2 partial pressure. Since the altered CO.sub.2 partial pressure can be ascertained tonometrically, tonometric monitoring is particularly valuable in surgical recovery units, intensive care units, and other settings. See for example, "The Role of Gut Mucosal Hyperfusion in the Pathogenesis of Post-operative Organ Dysfunction" by M. G. Mythen and A. R. Webb, Intensive Care Medicine (1994), 20:203-209 and "Gastric Intramucosal pH: A Non-invasive Measurement for the Indirect Measurement of Tissue Oxygenation" by Cinda H. Clark and Guillermo Gutierrez in American Journal of Critical Care (1992), 2:53-60.
A convenient and straightforward indication of the state of gut mucosal perfusion is the difference between a regional CO.sub.2 partial pressure measurement (PrCO.sub.2) obtained tonometrically from the organ and the systemic CO.sub.2 partial pressure, for example, that existing in arterial blood (PaCO.sub.2). See the PCT patent application and the Mythen et al. article, supra. Venous blood CO.sub.2 partial pressure (PvCO.sub.2) can also be used. An increase in the CO.sub.2 partial pressure difference, or the "CO.sub.2 gap", between the regional and systemic CO.sub.2 levels indicates a reduction in the adequacy of gut mucosal perfusion and the onset of dysoxia and/or other conditions hazardous to the patient.
The CO.sub.2 level of arterial blood is typically measured by periodically drawing a blood sample from the patient into a cuvette. The cuvette is then carried to, and placed in, a blood gas analyzer that uses, for example, electrochemical sensors, to measure the partial pressure of the sample. Or, a probe may be placed in an artery of the patient to obtain blood samples.
Because electrochemical sensors are temperature sensitive and because the temperature of the blood sample will change during transport to the blood gas analyzer, it has become conventional to correct blood CO.sub.2 partial pressure measurements to a standard temperature. Also, the blood CO.sub.2 partial pressure will vary with the temperature of the subject. For example, if the body temperature of the subject is reduced from the usual body temperature, a decrease in the partial pressure PaCO.sub.2 will occur, for a given amount of CO.sub.2 in the blood.
The use of a standard temperature permits data periodically obtained from a patient to be meaningfully compared even though the temperature of the patient changes in the course of time or permits data from a given patient to be compared to data obtained from other patients or compared to recognized criteria. Standard temperature arterial CO.sub.2 partial pressure values avoid confusion, as when a patient is attended by a number of physicians. For the foregoing reasons, use of standard temperature blood CO.sub.2 partial pressure values has become an accepted medical protocol. The standard temperature is typically 37.degree. (98.6.degree. F.), the normal temperature of the human body. The blood gas analyzer contains thermal control apparatus to ensure that the blood sample is at the standard temperature when the measurement of PaCO.sub.2 is made and contains a correction algorithm to correct the measurement to the actual temperature.
Recently, the use of gas as the tonometric sampling medium has come into use. Air may be used for this purpose. A gas analysis means, such as an infrared spectrometer, is connected directly to the tonometric catheter. The gaseous sampling medium is withdrawn from the sampling chamber of the tonometric catheter and passed through the gas analysis means, such as an infrared spectrometer, connected to the catheter to determine the regional CO.sub.2 partial pressure. The sampling medium withdrawn from the tonometer is at the existing actual temperature of the organ, which is usually the body temperature of the subject, and the regional CO.sub.2 partial pressure determination is thus made at that temperature.
The tonometrically obtained regional CO.sub.2 partial pressure (PrCO.sub.2) is compared to the arterial CO.sub.2 partial pressure (PaCO.sub.2) to determine the CO.sub.2 gap. This is currently done notwithstanding the fact that the regional CO.sub.2 partial pressure is an actual body temperature value whereas the arterial CO.sub.2 partial pressure is a standard temperature value. This use of values obtained for two different temperatures introduces the possibility of error in the determination of the CO.sub.2 gap.
For a normal person, the standard and actual body temperatures are the same (both 37.degree. C.) so that any errors are small or non-existent. But, actual body temperatures vary, and can vary over a wider range than is often appreciated. Fevers increase the actual body temperature above 37.degree. C., for example to 40.degree. C. (104.degree. F.). In many medical procedures, the temperature of a patient is deliberately reduced to slow metabolic functions, reduce swelling, or for other reasons. Reductions to a temperature of 30.degree. C. (86.degree. F.) may occur. Greater differences between actual body temperature of the subject and the standard temperature correspondingly increase the error in the determination of the regional-arterial CO.sub.2 partial pressure gap. These errors may result in inappropriate diagnosis and/or treatment of the subject.
The invasive and intermittent nature of obtaining direct arterial CO.sub.2 partial pressure measurements by periodically drawing blood or using probes has led to determining systemic CO.sub.2 levels non-invasively and continuously by using the exhaled respiration gases of the patient. Typically, the CO.sub.2 level existing at the end of exhalation, the end-tidal level (EtCO.sub.2), is used for this purpose. The end-tidal determination is carried out at actual body temperature.
In normal persons, the use of end tidal CO.sub.2 measurements in lieu of arterial blood CO.sub.2 measurements is usually appropriate since the gradient between the two is low and constant so that it is possible to determine the CO.sub.2 gap by a comparison of PrCO.sub.2 and PetCO.sub.2. However, for many persons, or for subjects in particular circumstances, such as mechanically ventilated patients, the correlation between PetCO.sub.2 and PaCO.sub.2 is lower. Further, unless the standard temperature PaCO.sub.2 value is compensated for the actual temperature of the subject, the gradient between PetCO.sub.2 and PaCO.sub.2 will change as the temperature of the subject changes. See "The Arterial to End-Tidal Carbon Dioxide Gradient Increases with Uncorrected PaCO.sub.2 Determination During Mild to Moderate Hypothermia", Christian Sitzwohl et al., Anesthesia Analc 1998; 86.
Concern over the use of end tidal CO.sub.2 for the foregoing reasons and/or a preference for a particular blood gas analysis protocol has lead some medical practitioners to prefer standard temperature blood gas analysis CO.sub.2 values, while others use actual temperature blood gas analysis values, while others use end-tidal CO.sub.2 values. This has, correspondingly, made obtaining CO.sub.2 gap measurements that are understood by, and acceptable to, medical practitioners difficult and has detracted from full realization of the usefulness of such measurements.